The long-range goal of this research is to regulate the loss of nitrogen and wasting complications associated with the juvenile-type of diabetes mellitus and other diseases. My approach to this problem is to identify and characterize the mechanisms used by living systems to degrade intracellular proteins and regulate the rate of degradation of specific enzymes, and proteins in general, according to the metabolic needs of the organism. One aspect of this research involves establishing how hormones influence the process of intracellular protein catabolism in particular tissues. In this proposed project the effects of alloxan-and streptozotocin-induced diabetes on turnover of glyceraldehyde-phosphate dehydrogenase and aldolase in liver and skeletal muscle will be assessed. The effects of insulin and glucagon administration on the turnover of these specific enzymes will also be measured. These studies will establish whether the turnover of these relatively long-lived cytosol proteins is accelerated in diabetic livers and whether these proteins are affected similarly in muscle. Arginase turnover will also be studied in liver and any changes in the enzyme turnover will be correlated with changes in the concentrations of branched chain amino acids. In studies on the initial events in the process of enzyme degradation, aldolase and glyceraldehyde-phosphate dehydrogenase and antibodies to these enzymes will be used to determine whether: a) inactive or modified forms of these enzymes exist in various compartments of normal and diabetic cells and b) modified forms of the enzymes have altered heat stabilities, altered susceptibilities to cellular proteases or altered propensities to associate with membranous elements of cells. In addition neutral cellular proteinase activities will be measured in normal and diabetic cells and their ability to degrade cellular proteins will be determined. The results of the proposed study should establish whether the negative nitrogen balance observed in diabetic animals is due in part to accelerated degradation of small, basic proteins and is associated with modifications of cellular enzymes and/or alterations of cellular proteinase activities.